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A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Bidirectional Mendelian randomization reveals that white matter tract alterations causally influence risk for 8 psychiatric disorders (risk changes: 2.2%- 71.4%) while alcohol use disorder increases WMT abnormality risk.

The authors report the mechanical stress-induced dielectric strength weakening of hBN nanosheets with thinner nanosheets showing more remarkable weakening, as evidenced by lower breakdown strength, shorter breakdown time, and larger leakage current.

Authors demonstrate that Ig-like binders targeting the C-terminal of α-synuclein fibrils block fibrils-induced pathological activities, including neuronal aggregation and neuroinflammation, suggesting potential molecular avenues for future Parkinson’s disease intervention.

Previous ophthalmic foundation models have struggled to generalize effectively to diverse and rare fundus diseases, restricting their clinical applicability. Here, the authors introduce a vision-language foundation model that demonstrates superior performance in diagnosing both common and rare fundus conditions.

An artificial ligament replacement is made from aligned carbon nanotubes formed into hierarchical helical fibres with nanometre and micrometre channels which are demonstrated for the replacement of anterior cruciate ligaments in both rabbit and ovine models, showing strong integration and functional recovery.

The development of three-dimensional (3D) covalent organic frameworks (COFs) with novel topologies is of both fundamental and practical interest but the construction of highly crystalline 3D COF remains challenging. Here, the authors report highly crystalline 3D COFs with pto and mhq-z topologies by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains.

Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.

TMEM16F is a Ca²⁺ activated ion channel and lipid scramblase involved in cell fusion. Here authors determine cryo-EM structures of TMEM16F with or without bound blockers, such as the FDA-approved drug niclosamide.

An implantable hydrogel-based phononic crystal that deforms with the surrounding tissues modifying the ultrasonic bandgap allows continuous and wireless monitoring of internal tissue strains.

The mechanisms that regulate the electrochemical equilibrium of condensates are not well understood. Now it has been shown that the aging process of biomolecular condensates can dynamically modulate the electrochemical equilibrium between phases, thereby affecting the physicochemical functions of condensates. This process potentially provides an active mechanism modulating intracellular ion flux.

The authors reveal that, in fruit fly ovaries, the protein Rhino is guided to specific regions of the genome by a combination of two histone modifications, enhancing understanding of how cells protect their DNA from harmful virus-like elements.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Tightly focused optical fields are essential in nano-optics, but lack tools for accurate yet efficient characterization. Here, the authors develop an in situ method to reconstruct the fully vectorial information of tightly focused fields in 3D space.

Lewis acid additive semicarbazide hydrochloride improves the formation of α-phase FAPbI₃-based films and promotes a homogeneous vertical distribution of A-site cations through a deprotonation–reprotonation process. The upgraded device performance reaches up to 26.12% with high stability, and mini-module perovskite solar cells achieving 21.47% (area, 11.52 cm²) demonstrate great scalability.

Recent work demonstrated control and readout of a superconducting qubit using a quadrature-biased electro-optic modulator. Here the authors report an alternative approach by biasing the modulator at the null point, which offers design simplifications and performance advantages.

Many countries are relying on land-based strategies to meet the climate targets set out in the Paris Agreement, putting pressure on land resources. Here the authors show a global reduction in cropland area under current climate pledges, with implications for trade and food security.

Yang et al. show an age-related increase in the microbial-derived metabolite phenylacetylglutamine that drives host cellular senescence by inducing DNA damage and mitochondrial dysfunction via ADR–AMPK signaling.

The underlying mechanisms for drug resistance in Acute Myeloid Leukemia (AML) are not completely understood. Here, the authors show that succinate accumulation, associated with succinate dehydrogenase deficiency, impairs the activity of the ubiquitin-conjugating enzyme UBC12 leading to tumor-promoting protein accumulation and drug resistance in AML.

Hydrogen-doping driven metal to ferroelectric phase transition in a complex oxide NdNiO₃ is demonstrated. Transient negative differential capacitance and implementation of polarization decay into neural network for learning are then presented.

Heterogeneous single-atom catalysts (SACs) offer high atom utilization and well-defined active sites but face challenges in multi-stage cross-couplings due to limited coordination and reactivity. Here, the authors introduce SACs on reducible carriers, enabling adaptive coordination to bypass oxidative addition in cross-couplings.

KRAS^G12D mutations frequently co-occur with mutated TP53 tumour suppressor in patients with pancreatic ductal adenocarcinoma (PDAC). Here the authors report the design of dual targeted therapeutic extracellular vesicles containing high copy numbers of TP53 mRNA and siKRAS^G12D, showing anti-tumor activity in PDAC preclinical models.

Stimulating endogenous cardiomyocyte proliferation offers a promising approach for treating cardiac injuries. Here, the authors demonstrate that Foxk1 and Foxk2 promote heart regeneration by enhancing cardiomyocyte proliferation through cell cycle activation and metabolic reprogramming, presenting potential therapeutic targets for ischemic heart disease

Aging-related immune alteration has been attributed to increased susceptibility to infection and cancer. Here the authors show, using both lung cancer samples and mouse models, that aged Treg cells express higher levels of an ER enzyme, SOAT2, have altered cholesterol metabolism, and induce CD8⁺ T cell senescence to dampen anti-tumor immunity.

Current brain organoids protocols face significant challenges in achieving adequate neural maturation to effectively replicate the functionality of mature neural circuits. Here, authors present an approach by integrating astrocyte-secreted factors to facilitate maturation and functional fidelity of in vitro brain organoids and planar neural cultures.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

The ectoenzyme CD73 is often elevated in tumour environments and targeting this protein is a tumour therapeutic target. Here the authors characterise a therapeutic anti-CD73 antibody cocktail which is more effective than either antibody alone and suggest a molecular mechanism of how this antibody cocktail functions.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Current brain-targeted delivery strategies using orthosteric sites of receptors is highly susceptible to cross-reactions limiting efficiency. Here, the authors report on the allosteric targeting of receptors to avoid this and demonstrate application in drug delivery across the blood brain barrier.

By tuning the plasma frequency, Yu, Gao et al. develop an industrial-scale chemical vapour deposition system for uniform nanocrystalline silicon oxide coatings, enabling 26.41% efficiency in silicon heterojunction solar cells with copper electrodes.

Synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells provide substantial enhancements in the expansion and potency of engineered human cytotoxic T cells.

Here, the authors perform a pan-genome-based genome-wide meta-analysis of six independent GWAS experiments in rice, demonstrating the potential of this approach to increase understanding of the genetic basis of, and genes underlying key rice traits.

Methanogenic hydrocarbon degradation can be carried out by archaea either by coupling alkane oxidation directly to methanogenesis, or in syntrophic associations with bacteria. Here, the authors provide experimental evidence supporting that methanogenic degradation of hydrocarbons can also be mediated by syntrophic cooperation between archaeal partners.

The 26S proteasome is a protein degradation machine composed of a 20S core particle (CP) flanked at one or both ends by a 19S ATPase regulatory particle (RP). Here the authors reconstitute asymmetric archaeal proteasomes and reveal allosteric coupling between the conformations of gates in the α-rings positioned at opposite ends of the CP, which modulates RP assembly and substrate entry.

The production of hematopoietic stem cells in the embryo is precisely regulated by various intrinsic and extrinsic factors. Here, the authors find that autophagy is involved in the maturation of hematopoietic precursors through nucleolin pathways.

Nucleosome-protein complexes stick to the air-water interface and denature upon plunge freezing for cryoEM. Here, authors Chio and Palovcak et al. develop EM grids that protect such complexes and use these grids to study the ATP-dependent chromatin remodeler SNF2h.